The long term objective of our current research is to understand the mechanisms by which cells move within a three-dimensional, multicellular mass. This movement is more complex than migration of an isolated cell on a flat substrate, because cells within a mass must gain traction on each other and also clear paths for themselves within and through the cell mass. We study such "3D cell motion" using time-lapse 3D microscopy which permits us to observe locomotion in living specimens over extended time periods. Two model systems are currently under study. The first is the movement of amoeboid cells within the multicellular mass of Dictyostelium, and the second is the migration of tumor cells in rat brains. To identify which molecules are important for motion within a cell mass, we compare the movement of normal and mutant cells and/or study the effects of drugs which alter the motion. Current research focuses on the role of the myosin II molecule in Dictyostelium locomotion and the hyaluronan receptor in brain tumor cell locomotion.